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Differential expression and parent-of-origin effect of the 5-HT2A receptor gene C102T polymorphism: analysis of suicidality in schizophrenia and bipolar disorder.

De Luca V, Likhodi O, Kennedy JL, Wong AH

Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behavior by a genetic association between the 5-HT2A C102T silent polymorphism and suicidality in patients with major depression. However, a recent meta-analysis failed to confirm this association. We developed an improved quantitative assay for the measurement of allele-specific expression of the 5-HT2A gene, and find that the ratio of C/T allele expression in the pre-frontal cortex of heterozygous suicide victims (n = 10) was significantly decreased in comparison with the non-suicide group (n = 10) (P = 0.049). Because the 5-HT2A gene is subject to imprinting, the parent-of-origin may affect the inheritance of suicidal behavior. Thus we examined the parental origin of specific alleles for genetic association in a genetic family-based sample of major psychoses in which information on suicidal behavior was available. No association between the 5-HT2A C102T polymorphism and suicidal behavior in major psychoses was detected with the transmission/disequilibrium test (TDT).

Published 2 April 2007 in Am J Med Genet B Neuropsychiatr Genet, 144(3): 370-4.
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